Crystalline solids are an essential part of our modern technological environment, since they are important components for many materials such as pharmaceuticals, foods, cosmetics, metals, ceramics and plastics. The customary way of forming crystals in the chemical industry is through suspension processes which rely on the use of solvents as media for homogenisation of the starting composition, and as an enabling environment for molecular assembly processes. Solvents have been found to influence crystallisation to the point of altering nucleation rates, crystal morphologies, crystal aggregation and the crystal structure of the end product. While significant progress has been made in understanding the origin of crystal morphology, our current knowledge of the molecular assembly processes leading to the nucleation of a particular crystal form in supersaturated solutions is poor. The work detailed in this final report deals with the role of solvent in nucleation processes and the mechanisms by which nucleation may be influenced by solvent choice.
The first part of the report deals with solution speciation in concentrated and supersaturated solutions and explores the link between the species present in solution and the crystal structure of the polymorph which nucleates. For this part of the study, carboxylic acids were selected as model materials and a combination of IR and Raman spectroscopy used identify the H-bonding motifs existing in their crystalline and solution phases. A significant portion of this work was devoted to the two monocarboxylic, tetrolic and benzoic acids and it was discovered that in some systems, for example tetrolic acid, there is a very clear link between the solution state of the molecule and its resulting crystal structures. In others, benzoic and mandelic acid it seem that irrespective of the state of the solute in solution it always nucleates the same structure.
The second portion of the work moves on from the nature of the solution to explore the impact of solvent on the nucleation process in the polymorphic system p-aminobenzoic acid (PABA). PABA has two crystalline polymorphic forms, and which are related enantiotropically having a transition temperature of 240C. It was thus envisaged that in this system the nucleation of the two forms could be studied at the transition temperature where thermodynamic effects would be identical for each and solvent influences could be systematically explored. Solvent selection was found to have a significant impact on the ability to nucleate the polymorph. Only in water was it possible to nucleate both forms; all other solvents favoured the form irrespective of the temperature. This outcome was rationalised in terms of the solution species and the impact of solvent on the growth of the phase.